FUT6促进胃癌细胞增殖、侵袭及迁移

FUT6 promotes the proliferation,invasion and migration of gastric cancer cells

目的 探究α1,3岩藻糖基转移酶-Ⅵ(FUT6)在胃癌中的表达及其对胃癌细胞增殖、侵袭及迁移的影响。方法 利用GEPIA网站、癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库分析FUT6在胃癌中表达情况,并分析其与肿瘤免疫的关系。通过Western blot检测胃癌细胞(MKN-45、MGC-803、BGC-823、SGC-7901、AGS)及胃黏膜上皮细胞(GES-1)中FUT6蛋白的表达水平,选取FUT6表达量最高的胃癌细胞进行后续实验。采用瞬时转染方式在SGC-7901细胞中构建FUT6下调的胃癌细胞系,然后通过CCK-8法检测细胞增殖能力,Transwell实验检测细胞侵袭、迁移能力,划痕实验检测细胞迁移能力,Western blot检测细胞转染效率及上皮间质转化(epithelial-mesenchymal transition, EMT)相关蛋白(E-cadherin、N-cadherin、Vimentin)变化。结果 FUT6在多种癌症中表达异常,在胃癌中表达显著升高(P<0.05),在胃癌组织中的表达显著高于癌旁组织(P<0.05);FUT6表达与胃癌免疫细胞、免疫刺激因子、免疫抑制因子、趋化因子及趋化因子受体和免疫检查点抑制剂具有相关性(P<0.05)。与GES-1细胞相比,FUT6在胃癌细胞(MKN-45、MGC-803、BGC-823、SGC-7901、AGS)中表达增加,差异具有统计学意义(P<0.05)。敲低FUT6后,SGC-7901细胞增殖率显著下降(P<0.05),细胞迁移距离减少(P<0.05),E-cadherin蛋白表达量升高,N-cadherin、Vimentin蛋白表达量降低(P<0.05)。结论 FUT6在胃癌中高表达,且参与胃癌患者免疫微环境。敲低FUT6可抑制胃癌细胞增殖、侵袭与迁移,此过程可能与EMT有关。

Objective To investigate the expression ofα1,3 fucosyltransferase-Ⅵ(FUT6)in gastric cancer and its effects on the pro-liferation,invasion and migration of gastric cancer cells.Methods GEPIA website and The Cancer Genome Atlas(TCGA)database were used to investigate the expression of FUT6 in gastric cancer and analyze its relationship with tumor immunity.The protein expres-sion level of FUT6 in gastric cancer cell lines(MKN-45,MGC-803,BGC-823,SGC-7901,AGS)and gastric mucosal epithelial cell line(GES-1)was detected by Western blot to screen the cells with the highest FUT6 expression for the further experiments.SGC-7901 cells with low FUT6 expression were constructed by transient transfection.The cell proliferation ability was detected by CCK-8 method,the cell invasion and migration abilities were detected by Transwell assay,the cell migration ability was detected by scratch assay,and the cell transfection efficiency and the expressions of epithelial mesenchymal transition(EMT)-related proteins(E-cadherin,N-cadherin,Vimentin)were detected by Western blot.Results The expression of FUT6 was abnormal in various cancers,and the expression of FUT6 in gastric cancer was significantly increased(P<0.05).The expression of FUT6 in gastric cancer tissues was significantly higher than that in adjacent tissues(P<0.05).The expression of FUT6 was correlated with immune cells,immunostimulators,immunosup-pressors,chemokines,chemokine receptors and immune checkpoint inhibitors in gastric cancer(P<0.05).FUT6 expression was significantly higher in gastric cancer cells(MKN-45,MGC-803,BGC-823,SGC-7901 and AGS)than in GES-1 cells(P<0.05).After FUT6 knockdown,the proliferation rate of SGC-7901 cells was significantly decreased(P<0.05),the cell migration distance was decreased(P<0.05),the expression of E-cadherin protein was increased(P<0.05),and the expressions of N-cadherin and Vimentin proteins were decreased(P<0.05).Conclusion FUT6 is highly expressed in gastric cancer and participates in the immune microen-vironment of patients with gastric cancer.Knockdown of FUT6 can inhibit the proliferation,invasion and migration of gastric cancer cells,which may be related to EMT.